Saturday, January 25, 2014

A colleague, recently starting as an assistant professor, with
a new laboratory and bright young graduate students, seemed unusually
stressed. I pried, guessing that in the
month of January the well of worry for most biomedical scientists is the
looming deadline for submission of grant proposals to the National Institutes
of Health. With exacerbation, he said: “The
funding line is now less than 10%. How
do I keep my lab open?”

These days this is a common question, even in elite
universities. Each year tens of thousands
biomedical scientists send in a new R01 proposal to the NIH, competing for that
small piece of the US budget that has been set aside to fund ‘curiosity-driven’
basic research --- research conducted by independent, often single
investigators. These proposals represent
a most remarkable channel for which a small portion of the US budget is allocated:
the government allows scientists with a laboratory that houses often only a few
students to describe their idea, and then have the peers of those scientists
evaluate these ideas and rank them, funding the top 10% or so.

In contrast to this curiosity-driven basic research is the ‘mission-driven’
research that the government funds, focusing on themes like the Human Genome Project,
or the Brain Mapping Project, organized efforts to answer a specific question. My young friend was facing the existential
struggle that is faced by all small, independent laboratories: to research
their own questions, rather than the ones that the government dictates. This struggle has a surprisingly long
history.

The day after the
bomb

On Tuesday, August 7, 1945, the New York Times printed in giant
letters: First atomic bomb dropped on Japan.
Below the headline were reports on speeches made by Truman and Churchill:
“New age ushered”, and the report that when the bomb was first tested, it had
vaporized a steel tower in the New Mexico desert. [A small advertisement on page 2 touted a Manhattan
bar that had just installed air conditioning, providing a cool relief from the
hot NY summer.]

But deep inside the newspaper, in the editorial section,
there was a paragraph that more than any other foretold the struggle that was
coming. Not the struggle for liberty and
the war against dictators and despots, but the struggle for funding of basic science
in the United States.

In its editorial section, the NY Times used the success of
the Manhattan project to exemplify the merits of organized, mission-driven
research “after the manner of industrial laboratories.” It used the success of the bomb to lambast
university professors that held that “fundamental research is based on
curiosity”. It concluded that the path
forward was for the government to state the problem, and then solve it by “team
work, by planning, by competent direction and not by a mere desire to satisfy
curiosity.”

The Manhattan project set a shining example. Why not do the same for other important
problems? Why not a Manhattan project to
cure heart disease, or Parkinson’s disease?

The struggle to fund
curiosity driven research

Just two weeks before the bomb was exploded a report first
commissioned by President Roosevelt but with his untimely death, now sent to President
Truman, had expressed a different view, one that championed curiosity driven
research. In that July 1945 report,
titled Science, The Endless Frontier,
Vannevar Bush had written: “Basic science is performed without thought of
practical ends, and basic research is the pacemaker of technological
improvement.”

Vannevar Bush, Dean of engineering at MIT from 1932-38,
convinced President Roosevelt to form the National Defense Research Committee
to coordinate scientific research for national defense, which he served as
chairman. By 1941, NDRC became part of
Office of Scientific Research and Development, which coordinated the Manhattan
Project. OSRD, under Bush’s
directorship, did something revolutionary: scientists were allowed to be ‘chief
investigators’ on projects related to the war effort. Rather than working in a national lab, or
being employed by the government, they would stay at their universities,
assemble their own staff, use their own laboratories, and then make periodic
reports to committees at OSRD. James
Conant, a member of one of these committees, would later write: “Bush’s
invention insured that a great portion of the research on weapons would be
carried out by men who were neither civil servants of the federal government
nor soldiers.” This idea fundamentally
changed research in the US, de-centralizing it, moving it away from industrial
and government labs, and placing it at universities.

In 1944, as the war in Europe neared its end, Bush was
called into Roosevelt’s office and there, the President asked him: “What’s
going to happen to science after the war?” Bush replied: “It’s going to fall
flat on its face.” The President replied: “What are we going to do about
it?”

In November 1944, this question was put down formally in a
letter from Roosevelt to Bush and OSRD.
The letter asked four questions: 1) How would the US make its scientific
achievements of the war years “known to the world” in order to “stimulate new
enterprises, provide jobs, … and make possible great strides for the
improvement of the national well-being”? 2) How would medical research be
encouraged? 3)How could the government aid private and public research, and how
should the two be interrelated? and 4) How could the government discover and
develop the talent for scientific research in America’s youth?

Bush believed that advances in fundamental science had paid
off spectacularly, resulting in new weapons and new medicines. “[He] believed that you had to stockpile
basic knowledge that could be called upon ultimately for its practical
applications, and that without basic knowledge, truly new technologies were
unlikely to emerge.”

Bush’s ideas took hold, eventually leading to establishment
of the National Science Foundation and the NIH, and the current mechanisms that
fund basic science in the US. But the
question persisted: should scientists be allowed to define their own questions
in basic science, or should the government organize them into teams that go
after mission-driven problems?

From pond scum to the
human brain

In 1979, in a Scientific
American article, Francis Crick (co-discoverer of DNA) suggested that a
fundamental problem in brain sciences was to control a single neuron. He speculated that if single neurons could be
controlled, particularly in the mammalian brain, a critical barrier would be
crossed to understand both the function of each region of the brain, and the
mechanisms necessary to battle neurological disease.

Crick did not know it at the time, but basic
scientists, doing curiosity-driven research, had already found the key piece of
the puzzle in an unlikely place, pond scum.
There, in single cell microbes, there was evidence that light-sensitive
proteins regulate the flow of electric charge across the cell membrane
(allowing the microbe to respond to light and move its flagella). Thirty years later, building on these basic,
seemingly useless results, Karl Deisseroth put the puzzle pieces together,
showing how to use light to control single cells in the primate brain,
producing a new field of neuroscience called optogenetics.

In a 2010 article, summarizing the remarkable insights
gained by his work, Karl Deisseroth reflected on his findings. He wrote: "I have occasionally heard colleagues suggest that it would
be more efficient to focus tens of thousands of scientists on one massive and
urgent project at a time --- for example, Alzheimer’s disease --- rather than
pursue more diverse explorations.Yet
the more directed and targeted research becomes, the more likely we are to slow
overall progress, and the more certain it is that the distant and untraveled
realms of nature, where truly disruptive ideas can arise, will be utterly cut
off from our common scientific journey."

Sources

Jonathan R. Cole (2010) The Great American University: its
rise to preeminence, its indispensable national role, why it must be protected.
PublicAffairs.

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About Me

I was born in Iran and immigrated to the US at the age of 14. I was educated at Gonzaga University, University of Southern California, and finally MIT. I studied under the mentorship of Prof. Michael Arbib and Prof. Emilio Bizzi. I am currently Professor of Biomedical Engineering and Neuroscience, and the Director of the BME PhD Program at Johns Hopkins School of Medicine. I am a neuroscientist who uses mathematics to understand how the brain controls our movements.